Journal of Lipid Research
Volume 47, Issue 12, December 2006, Pages 2690-2700
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Research Article
Elovl3: a model gene to dissect homeostatic links between the circadian clock and nutritional statuss⃞

https://doi.org/10.1194/jlr.M600230-JLR200Get rights and content
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The ELOVL3 protein is a very long-chain fatty acid elongase found in liver, skin, and brown adipose tissues. Circadian expression of the Elovl3 gene in the liver is perturbed in mutant CLOCK mice but persists in mice with severe hepatic dysfunction. A reliance on an intact clock, combined with the refractoriness to liver decompensation and the finding of a robust sexually dimorphic pattern of expression, evince a particularly complex mode of transcriptional control. The Elovl3 gene upstream region was repressed by RevErbα and activated by sterol-regulatory element binding protein-1 (SREBP1) transcription factors. We propose that the temporal coordination of RevErbα and SREBP1 activities integrates clock and nutrition signals to drive a subset of oscillatory transcripts in the liver. Proteolytic activation of SREBP1 is circadian in the liver, and because the cycle of SREBP1 activation was reversed after restricting meals to the inactive phase of the day, this factor could serve as an acute sensor of nutritional state. SREBP1 regulates many known lipogenic and cholesterogenic circadian genes; hence, our results could explain how feeding can override brain-derived entraining signals in the liver. This mechanism would permit a rapid adjustment in the sequence of key aspects of the absorptive and postabsorptive phases in the liver.

fatty acid
elongase
sterol-regulatory element binding protein target genes
restricted feeding
daily rhythm
phase shift

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Published, JLR Papers in Press, September 26, 2006.

Abbreviations:

    ACC

    acetyl-coenzyme A carboxylase

    ACS

    acyl-CoA synthase

    G3PAT

    glycerol-3-phosphate acyltransferase

    iBAT

    interscapular brown adipose tissue

    PPAR

    peroxisome proliferator-activated receptor

    SREBP

    sterol-regulatory element binding protein

    STAT

    signal transducer and activator of transcription

    VLCFA

    very long-chain fatty acid

    ZT

    Zeitgeber time

s⃞

The online version of this article (available at http://www.jlr.org) contains additional supplemental data.

1

Present address of A. Anzulovich: Laboratorio de Bioquímica Molecular, Area de Química Biológica, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis CP5700, Argentina.